The major histocompatibility complex ("MHC") plays a central role in the immune system. Antigen-specific T cells recognize antigenic peptides in association with MHC class I or II molecules on the cell surface. Class I molecules consist of two noncovalently associated subunits: a highly polymorphic .alpha. heavy chain and a conserved .beta.2-microglobulin (".beta.2-M") light chain. Two of the three extracellular domains of the heavy chain, i.e., domains .beta.1 and .alpha.2, are folded into a "groove" structure which anchors an antigenic peptide for presentation to T cells.
Human class I molecules (or "complexes") have been refolded from E. coli-produced heavy chains and .beta.2-M subunits in the presence of synthetic peptides (Garboczi et al., Proc. Natl. Acad. Sci. USA, 89:3429-3433, 1992). The three-dimensional structures of such recombinant complexes as determined by X-ray crystallography are virtually identical to the structure of the class I molecule as isolated from human cells (Madden et al., Cell, 75:693-708, 1993; Bjorkman et al., Nature, 329:506-512, 1987). Further, subtype A0201* of HLA-A2 produced in E. coli and assembled with synthetic HIV-1 nonapeptides has been shown to elicit cytolytic CD8.sup.+ T cell responses (Walter et al., Int. Immunology, 9:451-459, 1997).
The classical class I gene family includes the highly polymorphic human class I molecules HLA-A, -B, and -C, and murine class I (i.e., H-2) molecules D, K, and L. A series of structural relatives (non-classical class I molecules) has been found in humans (e.g., HLA-E, -F, -G, -H, -I, and -J; and CD1) and mice (Q, T, M, and CD1) (Shawar et al., Annu. Rev. Immunol., 12:839-880, 1994). These molecules have the typical structure of an antigen-presenting molecule, where a polymorphic heavy chain is noncovalently associated with the conserved .beta.2-M subunit. The T cell repertoire reacting with these non-classical ligands has been characterized to only a limited extent.